Computer simulation of transport experiments, sedimentation velocity for example, has been developed to the point where calculated boundary shapes can be directly useful in detecting and describing self-association reactions of macromolecules. We propose to enlarge the capabilities and efficiency of the simulation technique so that it can be applied similarly to mixed association reactions among unlike subunits. Appropriate programs will evolve in a straightforward way from existing techniques used with concentration dependent mixtures. When simulation procedures have been developed, comparisons between simulated and experimental sedimentation velocity profiles will be combined with sedimentation equilibrium experiments in a thorough study of two biologically significant mixed association reactions. Mixed histones from chicken erythrocytes will be examined in a range of solvents from pH 5 and low salt, where H3-H4 tetramers and H2A-H2B dimers are the predominant species, to pH 7 and 2 M NaC1, where a heterotypic tetramer containing one chain of each kind is the favored product of the equilibrium. The formation of complexes between the Fe-protein and the Fe-Mo component of nitrogenase from Clostridium pasteurianum and Azotobacter vinelandii wil be examined similarly. The objective will be to resolve current disagreement as to whether the most probable stoichimetry for nitrogenase complexes is 1:1 or 2:1. In each system, studies of the mixed associations will be preceded by careful examination of possible self-associations of the individual components: H3-H4 and H2A-H2B for the histone system and Fe-protein and Fe-Mo protein for the nitrogenases.